K Yoshioka1, Y Yasuda2, T Kisukeda2, R Nodera2, Y Tanaka2, K Miyamoto2. 1. Central Research Lab., Research & Development Div., Seikagaku Corporation, Higashiyamato-shi, Tokyo, Japan. Electronic address: keiji.yoshioka@seikagaku.co.jp. 2. Central Research Lab., Research & Development Div., Seikagaku Corporation, Higashiyamato-shi, Tokyo, Japan.
Abstract
OBJECTIVE: To study the pharmacological effects of Gel-200, cross-linked hyaluronate. EXPERIMENTAL DESIGN: We examined the chondroprotective, anti-inflammatory and analgesic effects of Gel-200 in experimental animal models for osteoarthritis (OA) and in a human synovial sarcoma cell line and normal human articular chondrocytes. RESULTS: In the OA model, a single-dose intra-articular (IA) injection of Gel-200 significantly suppressed cartilage degeneration and reduced synovitis of the knee joint. In the joint pain model, Gel-200 significantly suppressed pain responses for 4 weeks after injection. The residual property of Gel-200 in the knee joint tissue was investigated in rabbits. The mean residual ratio of injected Gel-200 in the synovium was 3.3% (95% confidence interval [CI], 2.4-4.2) at 28 days after the injection. The long-lasting analgesic effect of Gel-200 might be explained by its high residual ratio in the joint. In addition, we investigated the mechanism of action of Gel-200 in a human synovial sarcoma cell line and normal human articular chondrocytes. Gel-200 inhibited IL-1β-induced production of MMP-1, 3 and 13 in human chondrocytes and production of prostaglandin E2 in human synoviocytes in a concentration-dependent manner, respectively. CONCLUSION: A single-dose IA injection of Gel-200 exerts chondroprotective and anti-inflammatory effects in the experimental OA model, and long-lasting analgesia in the joint pain model, suggesting the beneficial multimodal function of Gel-200 against symptomatic OA patients.
OBJECTIVE: To study the pharmacological effects of Gel-200, cross-linked hyaluronate. EXPERIMENTAL DESIGN: We examined the chondroprotective, anti-inflammatory and analgesic effects of Gel-200 in experimental animal models for osteoarthritis (OA) and in a humansynovial sarcoma cell line and normal human articular chondrocytes. RESULTS: In the OA model, a single-dose intra-articular (IA) injection of Gel-200 significantly suppressed cartilage degeneration and reduced synovitis of the knee joint. In the joint pain model, Gel-200 significantly suppressed pain responses for 4 weeks after injection. The residual property of Gel-200 in the knee joint tissue was investigated in rabbits. The mean residual ratio of injected Gel-200 in the synovium was 3.3% (95% confidence interval [CI], 2.4-4.2) at 28 days after the injection. The long-lasting analgesic effect of Gel-200 might be explained by its high residual ratio in the joint. In addition, we investigated the mechanism of action of Gel-200 in a humansynovial sarcoma cell line and normal human articular chondrocytes. Gel-200 inhibited IL-1β-induced production of MMP-1, 3 and 13 in human chondrocytes and production of prostaglandin E2 in human synoviocytes in a concentration-dependent manner, respectively. CONCLUSION: A single-dose IA injection of Gel-200 exerts chondroprotective and anti-inflammatory effects in the experimental OA model, and long-lasting analgesia in the joint pain model, suggesting the beneficial multimodal function of Gel-200 against symptomatic OA patients.
Authors: Angela Avenoso; Angela D'Ascola; Michele Scuruchi; Giuseppe Mandraffino; Alberto Calatroni; Antonino Saitta; Salvatore Campo; Giuseppe M Campo Journal: Inflamm Res Date: 2017-08-12 Impact factor: 4.575